Excerpt

Nervous system diseases and disorders are highly prevalent and substantially contribute to the overall disease burden. Despite significant information provided by the use of animal models in the understanding of the biology of nervous system disorders and the development of therapeutics; limitations have also been identified. Treatment options that are high in efficacy and low in side effects are still lacking for many diseases and, in some cases are nonexistent. A particular problem in drug development is the high rate of attrition in Phase II and III clinical trials. Why do many therapeutics show promise in preclinical animal models but then fail to elicit predicted effects when tested in humans?

On March 28 and 29, 2012, the Institute of Medicine Forum on Neuroscience and Nervous System Disorders convened the workshop “Improving Translation of Animal Models for Nervous System Disorders” to discuss potential opportunities for maximizing the translation of new therapies from animal models to clinical practice. The primary focus of the workshop was to examine mechanisms for increasing the efficiency of translational neuroscience research through discussions about how and when to use animal models most effectively and then best approaches for the interpretation of the data collected.

Contents

• THE NATIONAL ACADEMIES
• PLANNING COMMITTEE ON IMPROVING TRANSLATION OF ANIMAL MODELS FOR NERVOUS SYSTEM DISRODERS
• FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS
• Reviewers
• 1. Introduction and Overview
  • ORGANIZATION OF THE WORKSHOP AND SUMMARY
• 2. Evaluation of Current Animal Models
  • EXPECTATIONS FOR ANIMAL MODELS IN DRUG DEVELOPMENT
  • CHOICE AND VALIDATION OF ANIMAL MODELS FOR CENTRAL NERVOUS SYSTEM DRUG DISCOVERY
  • THE IMPACT OF PUBLICATION BIAS
• 3. Translation from Animal Models to the Clinic: Case Examples from Neuroscience Research
  • ANIMAL MODELS FOR ALZHEIMER’S DISEASE
  • ANIMAL MODELS FOR NEURODEGENERATION
  • ANIMAL MODELS FOR STROKE
  • ANIMAL MODELS FOR ADDICTION
  • ANIMAL MODELS FOR SCHIZOPHRENIA
  • ANIMAL MODELS FOR PAIN
  • ANIMAL MODELS ADDRESSING NEURODEVELOPMENT
• 4. Perspectives on Standardization
  • CHALLENGES TO STANDARDIZATION OF BEHAVIORAL MODELS
  • DEVELOPING TRANSLATABLE COGNITIVE ASSAYS
  • STANDARDIZATION FROM THE PERSPECTIVE OF ALZHEIMER’S DISEASE MODELS
  • DISCUSSION
• 5. Perspectives on Corresponding Animal and Clinical Endpoints
  • ROLE OF MATCHING ENDPOINTS
  • PREPULSE INHIBITION
  • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
  • IMPROVING BIDIRECTIONAL TRANSLATION FOR NERVOUS SYSTEM DISORDERS
• 6. Addressing the Translational Disconnect
  • DEVELOPING BETTER ANIMAL MODELS OF ETIOLOGY AND PATHOPHYSIOLOGY
  • EFFORTS TO ADDRESS THE TRANSLATIONAL DISCONNECT
• 7. Summary of Workshop Topics
  • CURRENT ANIMAL MODELS
  • DISORDER-FOCUSED BREAKOUT DISCUSSIONS
  • STANDARDIZATION
  • CORRESPONDING ANIMAL AND CLINICAL ENDPOINTS
  • THE BASIC AND CLINICAL SCIENCE GAP
  • CLOSING REMARKS
  • SUMMARY
• APPENDIXES
  • A References
  • B Workshop Agenda
  • C Registered Attendees

Rapporteurs: Diana E. Pankevich, Theresa M. Wizemann, Bruce M. Altevogt

This project was supported by contracts between the National Academy of Sciences and the Alzheimer’s Association; CeNeRx Biopharma; the Department of Health and Human Services’ National Institutes of Health (NIH, Contract No. N01-OD-4-2139) through the National Eye Institute, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, and NIH Blueprint for Neuroscience Research; Department of Veterans Affairs; Eli Lilly and Company; Fast Forward, LLC; Foundation for the National Institutes of Health; GE Healthcare, Inc.; GlaxoSmithKline, Inc.; Johnson & Johnson Pharmaceutical Research and Development, LLC; Lundbeck Research USA; Merck Research Laboratories; The Michael J. Fox Foundation for Parkinson’s Research; the National Science Foundation (Contract No. OIA-0753701); One Mind for Research; Pfizer Inc.; the Society for Neuroscience; and Wellcome Trust.

Suggested citation:

IOM (Institute of Medicine). 2013. Improving the utility and translation of animal models for nervous system disorders: Workshop summary. Washington, DC: The National Academies Press.

The views presented in this publication are those of the editors and attributing authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

NOTICE: The workshop that is the subject of this summary was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine.